A great challenge in diagnosing and treating hearing impairment comes from the fact that people with similar degrees of hearing loss may have different speech recognition abilities. Previous research has established that common forms of hearing loss arise from a mixture of inner- and outer-hair-cell damage. A conceptual framework that inner and outer hair cells contribute to hearing in fundamentally different ways motivates the general hypothesis that differences in the degree of inner- and outer-hair-cell dysfunction contribute to across-patient variability in speech perception. Recent psychophysical studies have suggested that listeners with sensorineural hearing loss have a reduced ability to use temporal fine-structure cues in speech perception. These studies have fueled an active debate about the role of temporal coding in normal and impaired hearing, and may have important implications for improving the ability of hearing aids and cochlear implants to restore speech perception in noise. The proposed neurophysiological experiments will provide valuable data by directly quantifying the effects of sensorineural loss on temporal coding in the auditory nerve. The effects of selective inner- or outer-hair-cell damage will be studied using ototoxic drugs. Noise-induced hearing loss will be used to study the more common case of mixed hair-cell damage. Histopathological analyses and functional response measures will be used to characterize hair-cell lesions in individual animals. Specific Aim 1 is to quantify the effects of selective hair-cell damage on within- and across-fiber temporal coding. Innovative analyses that avoid previous experimental limitations in the study of across-fiber temporal coding will be used to quantify fine-structure and envelope coding, as well as traveling-wave delays. Preliminary data support our hypothesis that sensorineural loss affects across-fiber coding of fine-structure more than within-fiber coding. Specific Aim 2 is to determine whether sensorineural loss affects neural coding of fine-structure and envelope cues in vocoded speech. Differences in the ability to understand vocoded speech between listeners with normal and impaired hearing have been used to suggest a perceptual deficit in the use of TFS cues. The physiological basis for these perceptual results is difficult to evaluate because narrowband cochlear filtering limits the ability to isolate fine-structure and envelope at the output of the cochlea. Neural cross-correlation coefficients will quantify directly the effects of sensorineural loss on the fidelity of fine-structure and envelope coding for vocoded speech in noise. Modeling supports the hypothesis that significant degradations occur in both fine-structure and envelope responses. Specific Aim 3 is to quantify the effects of sensorineural loss on temporal coding of fundamental frequency in concurrent complex tones. Listeners with hearing loss show a reduced ability to make use of voice-pitch differences to segregate two competing talkers. It is hypothesized that the ability to estimate the fundamental frequencies of two concurrent complex tones is degraded primarily due to the loss of temporal fine structure, rather than from degraded envelope coding of unresolved harmonics. PUBLIC HEALTH RELEVANCE: The long-term goal of the proposed work is to obtain a better understanding of the physiological bases for robust speech perception, which has important theoretical and clinical implications. The data collected in the proposed experiments will provide fundamental knowledge about the differential effects of inner ear damage on the neural coding of perceptually relevant sounds. This knowledge will benefit the development of diagnostic and rehabilitative strategies to improve the daily lives of people with hearing loss.